Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy.

ABSTRACT: How does a single amino acid mutation occurring in the blinding disease, Leber's hereditary optic neuropathy (LHON), impair electron shuttling in mitochondria? We investigated changes induced by the m.3460 G>A mutation in mitochondrial protein ND1 using the tools of Molecular Dynamics and Free Energy Perturbation simulations, with the goal of determining the mechanism by which this mutation affects mitochondrial function. A recent analysis suggested that the mutation's replacement of alanine A52 with a threonine perturbs the stability of a region where binding of the electron shuttling protein, Coenzyme Q10, occurs. We found two functionally opposing changes involving the role of Coenzyme Q10. The first showed that quantum electron transfer from the terminal Fe/S complex, N2, to the Coenzy

SUBMITTER: Fuller JT 

PROVIDER: S-EPMC10523484 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature